Enhancement of host susceptibility to lethal endotoxin shock by staphylococcal pyrogenic exotoxin type C

Abstract

Staphylococcal pyrogenic exotoxin (PE) type C enhanced the susceptibility of rabbits to lethal shock by endotoxin by as much as 50,000-fold. A graph of log PE type C dose used for pretreatment versus log 50% lethal dose of endotoxin gave a straight line with a slope of approximately-1. Rabbits that received PE type C alone showed fevers only, but those given both PE type C and endotoxin showed initial fever followed by hypothermia, labored breathing, diarrhea, evidence of vascular collapse, and finally death. When a PE type C dose of 3 ,ug/kg was used, pretreatment of the animals with PE for 2 h before giving the endotoxin was required to obtain maximal susceptibility. However, when 15 ,ug of PE type C per kg was utilized, the endotoxin could be given before, concurrently, or after PE type C. The capacity of PE type C to prepare rabbits for enhanced susceptibility to endotoxin was lost after 24 to 48 h. Animals could be protected from enhanced susceptibility to endotoxin by prior immunization with either PE type C or endotoxin. However, 30% of the rabbits which were immunized with PE type C failed to develop immunity, and after three injections of PE type C, these animals developed gram-negative bacteremia and succumbed. In addition, rabbits with diarrhea initially, possibly caused by Pasteurella infection, died less than 24 h after a single injection of PE type C.

Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation

“…It is known that activated T cells upregulate TLR2 on their surfaces, where it functions as a costimulatory receptor that enhances cytokine production in response to activation by an anti-CD3 antibody (Komai-Koma et al, 2004). Moreover, the TLR4 agonist LPS has been reported to enhance superantigen toxicity by 50 000 times in a rabbit model of toxic shock syndrome (Schlievert, 1982), and it is therefore tempting to speculate that the TLR2 agonistic properties of the M1 protein may also contribute to its potent effect on T cells. In a clinical setting also other TLR agonists, such as lipoteichoic acid and peptidoglycan, are likely to contribute to the overall inflammatory response.…”

Investigation of the role of the disulphide bond in the activity and structure of staphylococcal enterotoxin C1

“…Since the mutants produced in this study varied widely in their effects on both T ceils and monocytes. it was of interest to assess their ability to induce shock in a rabbit model, which simulates most of the symptoms of toxic shock syndrome (Kim and Watson, 1970;Schlievert, 1982). Wild-type SECI induced a typical temperature rise in the animals and also enhanced their susceptibility to lethal endotoxin shock {Fig, 10).…”

Staphylococcal enterotoxin A induction of pro‐inflammatory cytokines and lethality in mice is primarily dependent on MyD88

“…[13][14][15] It appears that SEA is more potent than other toxin serotypes such as staphylococcal enterotoxin B (SEB) or staphylococcal enterotoxin C 1 (SEC 1 ). 13 Although LPS enhances the lethality of SEA in vivo, [13][14][15][16] the mechanism underlying the synergistic induction of pro-inflammatory cytokine responses remains unclear. In earlier studies, binding of SE to MHC class II molecules on monocytes resulted in an increase in IL-1 and TNFa.…”